Infectious bursal disease (also known as IBD, Gumboro Disease, Infectious Bursitis and Infectious Avian Nephrosis) is a highly contagious disease of young chickens caused by infectious bursal disease virus (IBDV), characterized by immunosuppression and mortality generally at 3 to 6 weeks of age. It is economically important to the poultry industry worldwide due to increased susceptibility to other diseases and negative interference with effective vaccination. In recent years, very virulent strains of IBDV (vvIBDV), causing severe mortality in chickens, have emerged in Europe, Latin America, South-East Asia, Africa and the Middle East. Infection is via the oro-fecal route, with affected birds excreting high levels of the virus for approximately 2 weeks after infection.
IBDV is a double stranded RNA virus that has a bi-segmented genome and belongs to the genus Avibirnavirus of family Birnaviridae. There are two distinct serotypes of the virus, but only serotype 1 viruses cause disease in poultry. At least six antigenic subtypes of IBDV serotype 1 have been identified by in vitro cross-neutralization assay. Viruses belonging to one of these antigenic subtypes are commonly known as variants, which were reported to break through high levels of maternal antibodies in commercial flocks, and cause immune suppression.
The IBDV genome consists of two segments, A and B, which are enclosed within a nonenveloped icosahedral capsid. The genome segment B (2.9 kb) encodes VP1, the putative viral RNA polymerase. The larger segment A (3.2 kb) encodes viral proteins VP2, VP3, VP4, and VP5. Among them, VP2 protein contains important neutralizing antigenic sites and elicits a protective immune response and most of the amino acid (AA) changes between antigenically different IBDVs are clustered in the hypervariable region of VP2. Thus, this hypervariable region of VP2 has been the target for the molecular techniques applied for IBDV detection and strain variation studies.
The IBDV capsid protein exhibits structural domains that show homology to those of the capsid proteins of some positive-sense single-stranded RNA viruses, such as the nodaviruses and tetraviruses, as well as the T=13 capsid shell protein of the Reoviridae. The T=13 shell of the IBDV capsid is formed by trimers of VP2, a protein generated by removal of the C-terminal domain from its precursor, pVP2. The trimming of pVP2 is performed on immature particles as part of the maturation process. The other major structural protein, VP3, is a multifunctional component lying under the T=13 shell that influences the inherent structural polymorphism of pVP2. The virus-encoded RNA-dependent RNA polymerase, VP1, is incorporated into the capsid through its association with VP3. VP3 also interacts extensively with the viral dsRNA genome.
Clinical disease is associated to bird age with the greatest bursal mass, which occurs between 3 and 6 weeks of age. The greatest bursal mass is mostly a result of a large population of maturing IgM-bearing B-lymphocytes (lymphoblasts), the main target of infection. Young birds at around two to eight weeks of age that have a highly active bursa of Fabricius are more susceptible to disease. Birds over eight weeks are more resistant to challenge and typically will not show clinical signs unless infected by highly virulent strains.
The poultry vaccine industry currently makes inactivated IBDV vaccines for administration to breeder chickens. Vaccinating parent breeder flocks produces maternal immunity in the chicks and protects them during the first few weeks of life from infectious bursal disease (IBD). In many cases, the vaccines for IBD are prepared in young chicks rather than eggs or cell culture because the quality and quantity of the antigen is considered to be superior. This is an expensive and time consuming process. Furthermore, animal use issues have increased the risk of losing this source of high quality IBDV antigens. Using antigens produced in eggs or cell culture could reduce the potency and efficacy of these vaccines and thus increase IBD related morbidity, mortality and the cost of poultry meat and egg production.
Therefore, what is needed in the art are safe and effective vaccines that can be practically produced to prevent IBDV.